Sheep, wolf, or werewolf: Cancer stem cells and the epithelial-to-mesenchymal transition

•There are multiple routes to generate cells that exhibit the cancer stem cell phenotype.•Cancer stem cells can arise from normal progenitor/stem cells or via an epithelial-mesenchymal transition of cancer cells.•Cancer stem cells are less sensitive to standard chemotherapies than differentiated cancer cells.•The biological variation across different types of stem cells may necessitate distinct therapeutic strategies.

Multiple cancers contain subpopulations that exhibit characteristics of cancer stem cells (CSCs), the ability to self-renew and seed heterogeneous tumors. Recent evidence suggests two potentially overlapping models for these phenotypes: one where stem cells arise from multipotent progenitor cells, and another where they are created via an epithelial to mesenchymal transition. Unraveling this issue is critical, as it underlies phenomena such as metastasis and therapeutic resistance. Therefore, there is intense interest in understanding these two types of CSSs, how they differ from differentiated cancer cells, the mechanisms that drive their phenotypes, and how that knowledge can be incorporated into therapeutics.